Side effects from currently available HIV treatment options are prevalent, adversely impact quality of life (QOL), and are associated with non-adherence to medications. Side effects management and coping interventions represent an unexplored avenue for improving QOL and adherence to treatment. Surprisingly, there are no published trials of interventions that primarily focus on reducing the impact of side effects from antiretroviral therapies. Building on an NIH funded career development award in the area of coping with HIV symptoms and treatment side effect, we propose in this revised application a randomized clinical trial (RCT) of a piloted, theory-based, empirically supported side effects management intervention with 278 HIV+ men and women on highly active antiretroviral therapy (HAART). This novel, one-on-one, five-session intervention will be administered by trained HIV clinical staff and will aim to enhance QOL and medication adherence as compared with a wait list control group receiving standard care. The intervention, guided by recent developments in Stress and Coping Theory, has been piloted and demonstrates high acceptability, feasibility, and promising changes in variables of interest. While we propose to test this intervention approach in the context of HIV treatment, the intervention was designed to be applicable to other illnesses in which treatment adverse reactions create coping challenges and threats to QOL.